Immune Regulation News Volume 7.04 | Feb 6 2015

IL-1 Signaling Modulates Activation of STAT Transcription Factors to Antagonize Retinoic Acid Signaling and Control the T_H17 Cell-iT_reg Cell Balance
Researchers found that interleukin 17 (IL-17) was needed to fully override retinoic acid-mediated expression of the transcription factor Foxp3 and induce protective helper T cell (T_H17) responses. [Nat Immunol] Abstract

MicroRNA-21 Promotes Th17 Differentiation and Mediates Experimental Autoimmune Encephalomyelitis
Investigators demonstrate that microRNA-21 (miR-21) expression is elevated in Th17 cells and that mice lacking miR-21 have a defect in Th17 differentiation and are resistant to experimental autoimmune encephalomyelitis. [J Clin Invest] Full Article

FOXP3⁺ Regulatory T Cell Development and Function Require Histone/Protein Deacetylase 3
Scientists determined that histone/protein acetyltransferases and histone/protein deacetylase (HDAC)3 mediates both the development and function of the two main Treg subsets, thymus-derived Tregs and induced Tregs. They determined that HDAC3 and FOXP3 physically interact and that HDAC3 expression markedly reduces Il2 promoter activity. [J Clin Invest] Full Article

Toll-Like Receptor Ligands Sensitize B-Cell Receptor Signaling by Reducing Actin-Dependent Spatial Confinement of the Receptor
Investigators describe a mechanism for receptor crosstalk in which receptor-induced increases in actin dynamics lower the threshold for signaling by another receptor. They show that the Toll-like receptor ligands lipopolysaccharide and CpG DNA, which are conserved microbial molecules, enhance signaling by the B-cell antigen receptor by activating the actin-severing protein cofilin. [Nat Commun] Full Article

Targeting Cell Surface ​TLR7 for Therapeutic Intervention in Autoimmune Diseases
Investigators show that ​Toll-like receptor 7 (​TLR7) is present on the cell surface of immune cells and that ​TLR7 responses can be inhibited by an anti-​TLR7 antibody. ​TLR7 responses in dendritic cells, macrophages and B cells are all inhibited by the anti-​TLR7 antibody. [Nat Commun] Abstract

IL-4 Abrogates T_H17 Cell-Mediated Inflammation by Selective Silencing of IL-23 in Antigen-Presenting Cells
Studying the impact of interleukin 4 (IL-4) on the polarization of human and mouse dendritic cells (DCs), scientists found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12-producing capacity of DCs, IL-4 completely abrogates IL-23. [Proc Natl Acad Sci USA]
Abstract | Full Article

Macrophages Eat Cancer Cells Using Their Own Calreticulin as a Guide: Roles of TLR and Btk
Researchers demonstrate that the activation of Toll-like receptor (TLR) signaling pathways in macrophages synergizes with blocking CD47 on tumor cells to enhance programmed cell removal. [Proc Natl Acad Sci USA] Abstract | Full Article

B-Lymphocyte-Mediated Delayed Cognitive Impairment following Stroke
The authors tested the hypothesis that a B-lymphocyte response to stroke could contribute to the onset of dementia. They discovered that, in mouse models, activated B-lymphocytes infiltrate infarcted tissue in the weeks after stroke. B-lymphocytes undergo isotype switching, and IgM, IgG, and IgA antibodies are found in the neuropil adjacent to the lesion. [J Neurosci] Abstract | Press Release

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Soligenix Announces Presentation and Poster
Soligenix, Inc. announced that it will be presenting preclinical data from two biodefense programs. [Press release from Soligenix, Inc. discussing research to be presented at the 2015 American Society of Microbiology (ASM) Biodefense and Emerging Diseases Research Meeting, Washington, DC] Press Release

Akaal Pharma Announces Positive Results from Phase I Clinical Study of Novel Topical AKP-11 for the Treatment of Psoriasis
Akaal Pharma Pty Ltd. announced the positive results from a randomized, double-blind, placebo-controlled Phase I clinical trial of AKP-11, a novel and first-in-class topical sphingosine 1-phosphate receptor-1 modulator for the treatment of mild-to-moderate plaque psoriasis. [Akaal Pharma Pty Ltd.] Press Release

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Stanford Launches Major Effort to Expedite Vaccine Discovery with $50 Million Grant
Stanford University announced that it has received a grant from the Bill & Melinda Gates Foundation to accelerate efforts in vaccine development. [Stanford University] Press Release

Crown Bioscience Announces a Key Expansion of Its Partnership with the National Resource Center for Mutant Mice (NRCMM) on Developing Novel Immuno-Oncology Mouse Models
The newly expanded strategic partnership will focus on the development of new immuno-oncology experimental cancer models, along with other models, including diabetes and inflammation diseases, to advance immuno-oncology translational research and the treatment of cancers and other diseases. [Crown Bioscience, Inc.] Press Release

Penn Medicine’s New Immunotherapy Study Will Pit PD-1 Inhibitor against Advanced Lung Cancer
Penn Medicine researchers have begun a new immunotherapy trial with the checkpoint inhibitor known as pembrolizumab in patients with oligometastatic lung cancer who have completed conventional treatments and are considered free of active disease but remain at a high risk for recurrence. [The University of Pennsylvania] Press Release

U.S. FDA Grants Breakthrough Therapy Designation for Roche’s Investigational Cancer Immunotherapy MPDL3280A (Anti-PDL1) in Non-Small Cell Lung Cancer
Roche announced that it has received a second Breakthrough Therapy Designation from the United States Food and Drug Administration (FDA) for its investigational cancer immunotherapy MPDL3280A. [Roche] Press Release

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Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

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Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Assistant/Associate Professor – Gastroenterology (North Carolina State University College of Veterinary Medicine)

Postdoctoral Position – Immunology Animal Models (The Technical University of Denmark)

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Postdoctoral Fellowship – CNS Inflammation (Rutgers University)

Senior Scientist – Immuno-Oncology (Merus B.V.)

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